The effects of signal erosion and core genome reduction on the identification of diagnostic markers

Jason W. Sahl, Adam J. Vazquez, Carina M. Hall, Joseph D. Busch, Apichai Tuanyok, Mark Mayo, James M. Schupp, Madeline Lummis, Talima R Pearson, Kenzie Shippy, Rebecca E. Colman, Christopher J. Allender, Vanessa Theobald, Derek S. Sarovich, Erin P. Price, Alex Hutcheson, Jonas Korlach, John J. LiPuma, Jason Ladner, Sean LovettGalina Koroleva, Gustavo Palacios, Direk Limmathurotsakul, Vanaporn Wuthiekanun, Gumphol Wongsuwan, Bart J. Currie, Paul S Keim, David M Wagner

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives. IMPORTANCE A comparative analysis of 1,130 Burkholderia genomes identified unique markers for many named species, including the human pathogens B. pseudomallei and B. mallei. Due to core genome reduction and signature erosion, only 38 targets specific to B. pseudomallei/mallei were identified. By using only public genomes, a larger number of markers were identified, due to undersampling, and this larger number represents the potential for false positives. This analysis has implications for the design of diagnostics for other species where the genomic space of the target and/or closely related species is not well defined.

Original languageEnglish (US)
Article numbere00846-16
JournalmBio
Volume7
Issue number5
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Sahl, J. W., Vazquez, A. J., Hall, C. M., Busch, J. D., Tuanyok, A., Mayo, M., Schupp, J. M., Lummis, M., Pearson, T. R., Shippy, K., Colman, R. E., Allender, C. J., Theobald, V., Sarovich, D. S., Price, E. P., Hutcheson, A., Korlach, J., LiPuma, J. J., Ladner, J., ... Wagner, D. M. (2016). The effects of signal erosion and core genome reduction on the identification of diagnostic markers. mBio, 7(5), [e00846-16]. https://doi.org/10.1128/mBio.00846-16